The objective of this contract is to understand the human host-pathogen response generated by infection or vaccination with respiratory bacteria and/or viruses. This information is needed in order to develop effective vaccination strategies against respiratory pathogens. To accomplish the objectives of this contract, the contractor will perform detailed immune studies in volunteers, following vaccine administration and, when appropriate pathogen challenge. Microbiologic and immunologic interactions between respiratory virus and bacteria will also be extensively evaluated, as will strategies for the early diagnosis of pneumonia. Further efforts will be made through iterative methodology to maximize that protective aspect of the immune response through the use of various adjuvants, delivery systems, dosing schedules or other methods. It is further intended that the contractor will interact effectively and frequently with a second contractor working on equivalent studies of enteric pathogens. It is anticipated that synergistic effects will be achieved by these two groups in the furthering of our understanding of the human mucosal and systemic immune response. Such a result will likely benefit studies of diseases other than those associated with the respiratory or digestive systems. It is anticipated that these studies will lead to more effective vaccine strategies against a large number of infectious diseases.